This program aims at exploring in depth certain problems of cellular pathology, related to tissue degeneration and ageing. Special attention will be paid to the involvement of lysosomes. A concerted approach based on the combined use of modern morphological and biochemical techniques has been adopted. The program includes three distinct projects. Project I deals with the normal cellular mechanisms of protein breakdown and turnover, and their alterations with age and under certain pathological conditions. Project II is concerned with the characterization of subcellular particles in the arterial wall and their possible changes in atherosclerosis. Project III is directed towards a better understanding of cell-mediated immunity, in particular the subcellular modifications associated with the transformation of lymphocytes to cytotoxic killer cells. BIBLIOGRAPHIC REFERENCES: de Duve, C., Exploring cells with a centrifuge. Science, 1975, 189, 186-194. de Duve, C. La Pathologie Cellulaire. Verhandelingen van de Koninklyke Academie van Geneeskunde van Belgie, 1976. (in press).